Digital Commons Network^™

A Lifecycle Governance And Learning Health System Framework For Trustworthy, Generalizable, And Sustainable Human-Ai Partnership In Clinical Practice: Lessons From The Asthma-Guidance And Prediction System (A-Gps), Chung-Il Wi, Shauna Overgaard, Momin Malik, Dave Watson, Deepak Sharma, Jennifer Le-Rademacher, Dan Kelleher, Lu Zheng, Joshua Ohde, Brian Lynch, Ashwani Khurana, Sunghwan Sohn, Mahmoud M Aljuhani, Chris Carpenter, Manuel Arteta, Jason Greenwood, Martha Hartz, Randy Foss, Elif Polat, Imad Absah, Carla Davis, Meera Gupta, Lynnea Myers, Björn Nordlund, Cui Tao, Mark L Wieland, Christi Patten, Amie Jones, Prathibha Varkey, Brenna T Loufek, David E Vidal, Nari Gopala, Eric Klee, Vijay H Shah, John D Halamka, Matthew R Callstrom, Nicholas L Rider, Hongfang Liu, Constantin Aliferis, Vesna D Garovic, Young J Juhn

Faculty, Staff and Students Publications

The integration of artificial intelligence (AI) into clinical decision support (CDS) holds promise for proactive, personalized, and precision care. However, current understanding of how to establish trustworthy human-AI partnerships is in its infancy, despite its critical importance for implementing AI in healthcare. We present the Asthma-Guidance and Prediction System (A-GPS) as a case study of a practice-integrated AI platform that demonstrates how trustworthy, generalizable and sustainable AI can be developed, evaluated, and implemented in real-world asthma care. We describe major challenges and solutions based on our real-world experience during the process and offer the practical framework, approaches, tools and workflow …

Robust Magnetoelectric Backscatter Communication System For Bioelectronic Implants, Fatima Alrashdan, Joshua E Woods, Ellie C Chen, Wendy Tan, Zhanghao Yu, Wei Wang, Mathews John, Lukas Jaworski, Drew Bernard, Allison Post, Angel Moctezuma-Ramirez, Abdelmotagaly Elgalad, Kaiyuan Yang, Mehdi Razavi, Jacob T Robinson

Faculty, Staff and Students Publications

Wireless communication technologies for bioelectronic implants enable remote monitoring for diagnosis and adaptive therapeutic intervention without the constraints of wired connections. However, wireless data uplink from millimeter-scale devices deep in the body struggles to achieve low power consumption while maintaining large misalignment tolerances. Here, we report a passive wireless backscatter communication system based on magnetoelectric transducers that consumes less than 0.3 pJ/bit and achieves less than 1E-6 bit error rate at a distance of 55 mm while tolerating a misalignment of 10 mm. Using this robust data uplink, we designed a wireless cardiac sensing node that can transmit electrocardiogram signals …

Evaluating Lingualai: A Prospective Validation Of Ai-Based Real-Time Translation Against Certified Human Interpreters, Uday P Singh, Carlos A Jaimes Garcia, Gabriel M Aisenberg, Javier Barreda Garcia, Jessica A Hernandez-Chilatra, Cecilia Wang, Dalilah Reyes De Jesus, Eileen Whalen, Veronica Santos Canellas, Amanda R Falk Vargas, Brian O Rodriguez Echevarria, Martin J Citardi, Babatope O Fatuyi, Xiaoqian Jiang

Faculty, Staff and Student Publications

Limited English proficiency affects over 25 million people in the United States and is associated with disparities in healthcare access, safety, and outcomes. We conducted a prospective, within-subject, simulation-based comparison to evaluate whether an in-house AI application (LingualAI) achieves non-inferior translation quality versus certified medical interpreters in English-Spanish otorhinolaryngology encounters. Standardized clinician-patient scripts were translated by LingualAI and by certified interpreters, and bilingual clinicians rated anonymized audio across multidomain quality measures. Using a prespecified non-inferiority margin of 0.30 points (Human - AI) on 5-point scales, LingualAI met non-inferiority for 2 of 3 primary factors (terminology accuracy Δ = 0.07; adequacy …

Smart Pediatric Oncology Tracker Of Symptoms (Spots), A Web-Based Interface For The Pediatric Pro-Ctcae: Development And Usability Study, Stacey Crane, Deevakar Rogith, Melody Hellsten, Andrew D Miller, Jacqueline Castillo, Brandy Boeger, Susan Vidaurre, Stefanie Pieper, Cecile Nguyen, Duc Anh Thanh Huynh, Jessica Wooden, Amy Franklin, Karen Moody, Wenyaw Chan, Pamela S Hinds, Constance Johnson

Faculty, Staff and Student Publications

Background: Children undergoing cancer treatment experience a range of treatment-related toxicities that significantly affect quality of life and adherence to therapy. Current methods for symptom reporting rely heavily on clinician interpretation of caregiver or child verbal reports, which can result in incomplete or inaccurate records. The Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Pediatric PRO-CTCAE; National Cancer Institute) provides a validated mechanism for direct symptom reporting by children and caregivers, yet its traditional administration and preselection of questions limit the breadth of symptom capture.

Objective: This research aimed to co-design and conduct formative usability testing …

Postapproval Study For Brain-Responsive Neurostimulation For Drug-Resistant Focal Epilepsy: Three-Year Efficacy And Interim Safety Results, Dawn Eliashiv, Vikram R Rao, Barbara C Jobst, Jerzy P Szaflarski, John D Rolston, Lesley C Kaye, Taneeta Mindy Ganguly, Katie Bullinger, Patricia C Dugan, David E Burdette, Angela Y Peters, Atif Sheikh, Kevin F Haas, Dileep R Nair, Lilit Mnatsakanyan, Imran H Quraishi, Meriem K Bensalem-Owen, Rns System Pas Study, Michael J Doherty, Babak Razavi, Tiffany L Fisher, Christopher Skidmore, Pradeep N Modur, Tawnya M Constantino, Vicenta Salanova, Andrew J Cole, Olga Taraschenko, Angelica Rivera-Cruz, James W Wheless, Nitin Tandon, Antoaneta Balabanov, Sami Aboumatar, Itzhak Fried, Cornelia Drees, Hae Won Shin, Zeenat Jaisani, Stephanie E Maciver, Sanjay E Patra, Edward F Chang, Jon T Willie, Ryder Gwinn, Travis Stoub, John M Stern, Tami Crabtree, Cairn G Seale, Sharon C Mcfadden, Jacob F Norman, Lise Johnson, Martha J Morrell

Faculty, Staff and Student Publications

Background and objectives: Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT.

Methods: This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will …

Water-Soluble Fullerene Derivatives Mitigate Cranial Radiation-Induced Neuroinflammation And Cognitive Dysfunction, Naren Gundapaneni, Iona Hill, Lydia W T Cheung, Khadijeh Koushki, Alyssa Fausnaught, Phuoc Minh Quan Mai, Arjun Vasan, Prapannajeet Biswal, Ashutosh Tripathi, Anilkumar Pillai, Vijayasree V Giridharan, Tatiana Barichello, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

Radiotherapy is widely used to treat malignant and benign brain tumors. A major constraint, however, is the low tolerance of normal brain tissue to radiation. Cranial irradiation-induced injury manifests as inflammatory responses and neurodegeneration, which jointly contribute to progressive cognitive decline. These complications can restrict the delivery of optimal therapeutic doses, cause persistent neurological symptoms, and ultimately compromise quality of life. Thus, neuroprotective agents have emerged as a strategy to safeguard normal tissues from radiation-induced neurotoxicity. This study investigated the efficacy of a highly soluble [60]fullerene (C60) derivative, C60-ser, a carbon-based nanomaterial, to mitigate radiation-induced brain injury. Oral administration of …

Correction: Berezowski Et Al. Biomarkers In Renal Cell Carcinoma: A Systematic Review And Immunohistochemical Validation Study, Brett Berezowski, Robert Boothe, Billy Chaplin, Sharon J Del Vecchio, Zakariya Fares, Tyrone L R Humphries, Keng Lim Ng, Taylor Noonan, Hemamali Samaratunga, Aaron Urquhart, David A Vesey, Simon T Wood, Glenda C Gobe, Robert J Ellis

Faculty, Staff and Student Publications

This corrects the article "Biomarkers in Renal Cell Carcinoma: A Systematic Review and Immunohistochemical Validation Study" in volume 17, 2588.

Animal Models Of Delirium: A Narrative Review, Tatiana Barichello, Carla Sasso Simon, Diogo Dominguini, Cristiane Ritter, Tsuyoshi Nishiguchi, Gen Shinozaki, Felipe Dal-Pizzol

Faculty, Staff and Student Publications

Delirium is an acute cognitive failure characterized by an acute onset and psychomotor disturbances. It is associated with poor outcomes in hospitalized patients, resulting in prolonged hospital stays, elevated rates of mortality, and cognitive dysfunctions after hospital discharge. The pathophysiology of delirium remains poorly understood, making the development of animal models a promising avenue for researchers to elucidate the mechanisms underlying human delirium. These models not only aid in understanding the pathophysiology and etiology of the disease but also enhance the efficacy of nonpharmacological interventions and identify pharmacological therapies. This review aims to present the most relevant and translational animal …

Natural History Of Ngly1 Deficiency: Motor Function & Clinical Features, Grace Morrison, Selina Dwight, Hal Landy, William F Mueller, Pam Ventola, Regina Deck, Becky Schweighardt, Matt Wilsey, Kevin J Lee, Bernhard Suter

Faculty, Staff and Students Publications

N-glycanase 1 (NGLY1) Deficiency is an ultra-rare neurodevelopmental disorder caused by biallelic loss-of-function mutations in the NGLY1 gene, leading to severe impairments in neurocognitive and motor function abilities in the affected patient population. Its core clinical features include global developmental delay, hyperkinetic movement disorders, elevation of liver transaminases, (hypo)alacrima, and progressive sensorimotor neuropathy. Due to the range of phenotypes and severity within the confirmed patient population, ongoing characterization of the disease is critical. A prospective natural history study (NHS) was conducted to further elucidate disease phenotypes and examine any changes in neurocognitive or motor function over a one-year period. Fifteen …

Is2c2: A Cointelligent Platform For Mechanistic Discovery Of Disease Cellular Crosstalk, Jianting Sheng, Ju Young Ahn, Li Yang, Zhihao Wan, Shaohua Qi, Xiaohui Yu, Zhan Xu, Yuliang Cao, Matthew Vasquez, Amna Irfan, Yuanyuan Zhu, Hong Zhao, Zheng Yin, Ying Zhu, Yunfeng Ding, Alireza Faridar, Lin Wang, Fengshuo Liu, Hongxia Wang, Zhigang Ji, Dongxue Mao, Michael Chan, Daniel Kermany, Wenjuan Dong, Doo Yeon Kim, Xiang H-F Zhang, Stephen T C Wong

Faculty, Staff and Students Publications

Large language models (LLMs) have demonstrated impressive capabilities in summarization, reasoning, and content generation, yet their inability to directly interpret large-scale omics data has limited their utility in data-driven hypothesis generation-particularly in mechanism discovery that demands the integration and interpretation of multimodal datasets, heterogeneous models, and deep domain expertise. Conversely, traditional computational algorithms excel at quantitative analysis of omics data but often rely heavily on labor-intensive, expert-driven interpretation to extract biologically meaningful insights. Here, we introduce (cointelligent single-cell spatial cell‒cell communication: iS2C2), a novel cointelligent platform that synergizes mathematically rigorous computational algorithms with the contextual reasoning capabilities of LLMs to …

Identifying Novel Gene Dysregulation Associated With Opioid Overdose Death: A Meta-Analysis Of Differential Gene Expression In Human Prefrontal Cortex, Javan K Carter, Bryan C Quach, Caryn Willis, Melyssa S Minto, Dana B Hancock, Janitza Montalvo-Ortiz, Olivia Corradin, Ryan W Logan, Consuelo Walss-Bass, Brion S Maher, Eric Otto Johnson

Faculty, Staff and Student Publications

Only recently have human postmortem brain studies of differential gene expression (DGE) associated with opioid overdose death (OOD) been published; sample sizes from these studies have been modest (N = 40-153). To increase statistical power to identify OOD-associated genes, we leveraged human prefrontal cortex RNA-seq data from four independent OOD studies and conducted a transcriptome-wide DGE meta-analysis (N = 272). Using a unified gene expression data processing and analysis framework across studies, we meta-analyzed 20, 098 genes and found 335 significant differentially expressed genes (DEGs) by OOD status (false discovery rate <  0.05). Of these, 66 DEGs were among the list of 303 genes reported as OOD-associated in prior prefrontal cortex molecular studies (e.g., genes/gene families OPRK1, NPAS4, DUSP, EGR). The remaining 269 DEGs were not previously reported (e.g., NR4A2, SYT1, HCRTR2, BDNF). There was little evidence of genetic drivers for the observed differences in gene expression between opioid addiction cases and controls. Enrichment analyses for the DEGs across molecular pathway and biological process databases highlight an interconnected set of genes and pathways linked to orexin and tyrosine kinase receptors through MEK/ERK/MAPK signaling to affect neuronal plasticity.

Dna Methylation Signatures Associated With Bipolar Disorder In Peripheral Blood Improve Prediction Models, Markos Tesfaye, Anne-Kristin Stavrum, Kira D Höffler, Kevin S O'Connell, Friederike S David, Melanie E Garrett, Sonia Hesam-Shariati, Bronwyn J Overs, Claudia Pisanu, Luana Spano, Oliver J Watkeys, Antoine Weihs, Rafaella Ardau, Allison E Ashley-Koch, Lavinia Athanasiu, Jean C Beckham, Kyle J Bourassa, Caterina Chillotti, Srdjan Djurovic, Ole K Drange, Josef Frank, Anouar Khayachi, Nathan A Kimbrel, Lourdes Martorell, Susanne Meinert, Ingrid Melle, Gunnar Morken, Pasquale Paribello, Marco Pinna, Gloria Roberts, Guy Rouleau, Peter R Schofield, Esteban Sepúlveda, Giovanni Severino, Vidar M Steen, Frederike Stein, Fabian Streit, Va Mid-Atlantic Mirecc Workgroup, Trine Vik Lagerberg, Martin Alda, Udo Dannlowski, Andreas J Forstner, Janice M Fullerton, Hans J Grabe, Melissa J Green, Tilo Kircher, Javier Labad, Mirko Manchia, Philip B Mitchell, Jair C Soares, Alessio Squassina, Alexander Teumer, Leonardo Tondo, Elisabet Vilella, Ole A Andreassen, Boris Chaumette, Gabriel R Fries, Stephanie Le Hellard

Faculty, Staff and Student Publications

Background: Bipolar disorder (BD) is a major mood disorder influenced by both genetic and environmental factors. While DNA methylation from peripheral tissues can reflect both genetic and environmental influences and reveal insights into disease biology, it remains understudied in BD. DNA methylation signatures may complement polygenic scores (PGS) and hold potential as biomarkers. Here, we conducted the largest epigenome-wide association study (EWAS) of BD to date and evaluated the predictive value of polymethylation scores (PMS) in classifying case-control status.

Methods: DNA methylation from peripheral blood of 1729 cases and 1747 controls, comprising twelve cohorts, was obtained. We performed meta-analyses for …

Progressive Cardiac Phenotypes And Reduced Reversibility From Long-Term Cugexp Rna Expression In A Dm1 Mouse Model, Rong-Chi Hu, Mohammadreza Tabary, Xander Ht Wehrens, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is caused by an expanded CTG repeat in the DMPK gene, resulting in mutant transcripts that form expanded CUG (CUGexp) RNA foci and sequester muscleblind-like (MBNL) RNA-binding proteins. DM1 is multisystemic, with progressive worsening of disease manifestations in affected tissues. Disease progression is attributed to somatic expansion of the CTG repeats with age, resulting in production of CUGexp RNA with enhanced intrinsic toxicity due to increased MBNL sequestration. To determine the degree to which cardiac disease progression can occur independently of repeat expansion, we used a transgenic DM1 mouse model with inducible heart-specific expression of …

Development Of Novel Plasma Proteomic Biomarkers For Cancer-Associated Thrombosis In An Advanced Cancer Cohort, Preeti, Mrinal Ranjan, Dang Pham, Juan L Bueno, Micheline M Resende, Michael E Scheurer, Christopher I Amos, Chao Cheng, Ang Li

Faculty, Staff and Students Publications

Background: Existing risk models for cancer-associated thrombosis (CAT) show suboptimal performance in selective high-risk populations with cancer. Affinity-based plasma proteomics offers a novel approach for detecting CAT risk.

Objectives: To identify plasma biomarkers for CAT using proximity extension assays in an advanced cancer cohort.

Methods: We performed a nested case-control study using the Olink Explore HT panel. The final cohort included 57 patients with CAT and 113 matched control patients from 5 selected cancer types who had samples collected between cancer diagnosis and chemotherapy initiation. Random survival forest model was used to assess nonlinear associations with CAT in 5416 normalized …

Pharmacogenomic-Guided Prescribing And Polypharmacy Across Age Groups In Obsessive-Compulsive Disorder: A Retrospective Study, Sheldon R Garrison, Matthew W Boyer, Anthony W Zoghbi, Rachel A Schwartz, Nicolette Weisensel, Martin E Franklin, Madeline M Hartig, Maharaj Singh, Sreya Vadapalli

Faculty, Staff and Students Publications

Background: This study evaluated medication utilization in children, adolescents, and adults with obsessive-compulsive disorder (OCD), a chronic psychiatric condition characterized by intrusive thoughts and repetitive behaviors. Although first-line treatments include selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT), the heterogeneous biological underpinnings contribute to suboptimal outcomes, with 40-60% of individuals not responding to SSRIs. This complex phenotype often leads to psychotropic polypharmacy, which may be mitigated by incorporating combinatorial pharmacogenomic (PGx) testing into protocol-based care to identify potential gene-drug interactions.

Methods: A retrospective review was conducted of individuals with OCD aged 8 to 65 years who received either …

Genetic Analysis Of The X-Linked Adrenoleukodystrophy Gene Abcd1 In Drosophila Uncovers A Conserved Phenotype, Joshua Manor, Sharayu V Jangam, Hyung-Lok Chung, Pranjali Bhagwat, Jonathan C Andrews, Hillary Chester, Shu Kondo, Saurabh Srivastav, Juan Botas, Ann B Moser, Suzette M Huguenin, Michael F Wangler

Duncan NRI Faculty and Staff Publications

X-linked adrenoleukodystrophy (X-ALD) is a progressive neurodegenerative disorder caused by a loss-of-function (LOF) mutation in the ATP-binding cassette subfamily D member 1 (ABCD1) gene, leading to the accumulation of very long-chain fatty acids (VLCFAs). This disorder exhibits striking heterogeneity; some male patients develop an early childhood neuroinflammatory demyelination disorder, while other patients, including adult males and most affected female carriers, experience a chronic progressive myelopathy. Adrenocortical failure is observed in almost all male patients, with the age of onset varying, sometimes being the first diagnostic finding. The gene underlying this spectrum of disease encodes an ATP-binding cassette (ABC) transporter that …

Cd8+ T Cell Differentiation Into Nk-Like Effector Cells Drives Transplant Rejection, Dawei Zou, Stephanie G Yi, Yulin Dai, Luan Truong, Lillian W Gaber, Richard J Knight, Xiang Xiao, Rafik M Ghobrial, Xian C Li, Zhongming Zhao, Wenhao Chen, A Osama Gaber

Faculty, Staff and Student Publications

T cells are central drivers of transplant rejection, yet the differentiation fates underlying this process remain unclear. Using single-cell transcriptomic profiling of human kidney allograft biopsies, we identified a predominant infiltrating CD8+ T cell subset exhibiting killer cell lectin-like receptor (KLR)+ NK-like features. Mechanistic studies in mice showed that the KLR+ subset emerged de novo post-transplantation and dominated the CD8+ T cell infiltrate in rejecting allografts. These NK-like CD8+ T cells expressed high levels of interferon regulatory factor 4 (IRF4), and Irf4 deletion disrupted their differentiation and induced transplant acceptance. Therapeutically, either costimulation blockade or mTOR inhibition substantially reduced the …

Immediate Nerve And Tendon Transfers After Wide Resection Of A Radial Nerve Malignant Peripheral Nerve Sheath Tumor: A Case Report And Surgical Technique, Joanne Zhou, Sai Shreya Kambham, Andrew Fang, Christopher Frey, Michael Macavoy

Faculty, Staff and Student Publications

The authors have reported on immediate nerve and tendon transfers postresection of a radial nerve-based malignant peripheral nerve sheath tumor in a 15-year-old female with neurofibromatosis. The median nerve branch to flexor carpi radialis was transferred to the posterior interosseous nerve, the median nerve branch to flexor digitorum superficialis was transferred to the nerve to extensor carpi radialis brevis, and the pronator teres tendon was transferred to the extensor carpi radialis brevis tendon, with 3-year outcomes reported. Tumor excision, tendon, and nerve transfer yielded negative margins and remission. Functional wrist/finger extension appeared at 6 months and increased until 3 years …

Characterizing Core Outcomes Of Responsible Stewardship For Human Genomic Data In The Cloud, Vasiliki Rahimzadeh, Bronwyn Walsh, Heidi L Rehm, Mildred Cho, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

We present findings from a scoping review of the genomic data sharing literature used to inform a core outcomes set for responsible data stewardship in the cloud. Genomic and related health data stemming from government funded research have undergone mass migration to the cloud where they can be more securely stored, accessed, and analyzed within shared computing environments. While this migration reflects a shift in privacy and security infrastructure for cloud-based repositories as oversight becomes more globalized, it also necessitates new data stewardship responsibilities to align authorized data access with ethical data use. Responsible data stewardship refers to the ethical …

Applying User-Centered Design To Develop A Culturally Sensitive, Low-Calorie Meal Plan For Enhancing Dietary Behavioral Control In Masld, Maya Balakrishnan, Paola Martinez, Brett Deng, Ivonne Arguelles, Crystal Arguelles, Terri L Fletcher, Natalia I Heredia, Myriam Ibarra, Anna Christine Rome

Faculty, Staff and Students Publications

Background: Dietary changes are essential for managing metabolic dysfunction-associated steatotic liver disease (MASLD), yet patients often face barriers related to knowledge, skills, cost, time, and cultural fit.

Aims: The purpose of this paper is to report a process for culturally tailoring a dietary intervention and its application to create a calorie-restricted meal plan for Mexican and Central American patients with MASLD. Guided by the Theory of Planned Behavior and user-centered design, we produced a culturally tailored seven-day structured meal plan aligned with dietary guidelines for MASLD and weight loss.

Methods: We conducted a three-phase, mixed-methods process among Mexican/Central American patients …

Multi-Scale Data Improves Performance Of Machine Learning Model For Long Covid Identification, Christopher Guardo, Zhang Xinmeng, Srushti Gangireddy, Yan Chao, V Eric Kerchberger, Alyson L Dickson, Emily R Pfaff, Hiral Master, Xin Yi, Melissa Basford, Christopher G Chute, Nguyen K Tran, Salvatore Mancuso, Toufeeq Ahmed Syed, Zhao Zhongming, Feng Qiping, Melissa Haendel, Christopher Lunt, Paul A Harris, Li Lang, Geoffrey S Ginsburg, Joshua C Denny, Dan M Roden, Wei Wei-Qi

Faculty, Staff and Student Publications

Background: Long COVID affects a substantial proportion of the over 778 million individuals infected with SARS-CoV-2, yet predictive models remain limited in scope. While existing efforts, such as the National COVID Cohort Collaborative (N3C), have leveraged electronic health record (EHR) data for risk prediction and identification, accumulating evidence points to additional contributions from social, behavioral, and genetic factors.

Methods: Using a diverse cohort of SARS-CoV-2-infected individuals (n > 17,200) from the NIH All of Us Research Program, we investigated whether integrating EHR data with survey-based and genomic information improves model performance.

Results: Our multi-scale approach outperforms EHR-only model's area under the …

Large-Scale Genetic Characterization Of Parkinson’S Disease In The African And African Admixed Populations, Fulya Akçimen, Kimberly Paquette, Peter Wild Crea, Kathryn Step, Emily Waldo, Mathew J Koretsky, Paula Saffie-Awad, Charles Achoru, Funmilola Taiwo, Simon Ozomma, Gerald Onwuegbuzie, Marzieh Khani, Spencer Grant, Lukman Owolabi, Chiamaka Okereke, Olajumoke Oshinaike, Emmanuel Iwuozo, Suleyman Can Akerman, Paul Suhwan Lee, Shyngle Oyakhire, Nosakhare Osemwegie, Kensuke Daida, Sani Abubakar, Adedunni Olusanya, Mariam Isayan, Christiane Alvarez, Rami Traurig, Adebimpe Ogunmodede, Sarah Samuel, Mary B Makarious, Fadimatu Sa'ad, Rashidat Olanigan, Kristin Levine, Ewere Marie Ogbimi, Dan Vitale, Francis Odiase, Francis Ojini, Olanike Odeniyi, Zih-Hua Fang, Nkechi Obianozie, Deborah A Hall, Ernest Nwazor, Tao Xie, Francesca Nwaokorie, Mahesh Padmanaban, Paul Nwani, Ejaz A Shamim, Alero Nnama, David Standaert, Morenikeji Komolafe, Marissa Dean, Godwin Osaigbovo, Elizabeth Disbrow, Ismaila Ishola, Ashley Rawls, Frank Imarhiagbe, Shivika Chandra, Cyril Erameh, Vanessa Hinson, Naomi Louie, Ahmed Idowu, J Solle, Scott A Norris, Abdullahi Ibrahim, Camilla Kilbane, Gauthaman Sukumar, Lisa M Shulman, Daniel Ezuduemoih, Julia Staisch, Sarah Breaux, Clifton Dalgard, Erin R Foster, Abiodun Bello, Andrew Ameri, Raquel Real, Erica Ikwenu, Huw R Morris, Roosevelt Anyanwu, Erin Furr Stimming, Kimberley Billingsley, Wemimo Alaofin, Pilar Alvarez Jerez, Osigwe Agabi, Dena G Hernandez, Rufus Akinyemi, Sampath Arepalli, Laksh Malik, Raymond Owolabi, Yakub Nyandaiti, Hampton L Leonard, Kolawole Wahab, Oladunni Abiodun, Carlos F Hernandez, Fatima Abdulai, Hirotaka Iwaki, Soraya Bardien, Christine Klein, John Hardy, Henry Houlden, Kamalini Ghosh Galvelis, Mike A Nalls, Nabila Dahodwala, Whitley Aamodt, Emily Hill, Alberto Espay, Stewart Factor, Chantale Branson, Cornelis Blauwendraat, Andrew B Singleton, Oluwadamilola Ojo, Lana M Chahine, Njideka Okubadejo, Sara Bandres-Ciga

Faculty, Staff and Student Publications

Elucidating the genetic contributions to Parkinson's disease aetiology across diverse ancestries is a critical priority for the development of targeted therapies in a global context. We conducted the largest sequencing characterization of potentially disease-causing, protein-altering and splicing mutations in 710 cases and 11 827 controls from genetically predicted African or African admixed ancestries. We explored copy number variants (CNVs) and runs of homozygosity in prioritized early onset and familial cases. Our study identified rare GBA1 coding variants to be the most frequent mutations among patients with Parkinson's disease, with a frequency of 4% in our case cohort. Of the 18 …

Timing Isn't Everything: Rethinking Mortality Risk In Type A Aortic Dissection Surgery, Anna H Xue, Joseph S Coselli

Faculty, Staff and Students Publications

No abstract provided.

Purine Metabolic Adaptation Protects The Endothelium From Disturbed Flow-Induced Dna Damage And Atherosclerosis, Qian Ma, Yongfeng Cai, Zhidan Zhang, Dingwei Zhao, Yuan Zhao, Peishan Xu, Tammy Lu, Wendy Zhang, Qiuhua Yang, Yaqi Zhou, Varadarajan Sudhahar, Tohru Fukai, Hanjoong Jo, Yiming Xu, Yuqing Huo

Faculty, Staff and Students Publications

Despite effective lipid-lowering therapies, atherosclerosis continues to be a leading cause of death, with considerable residual cardiovascular risk. Atherosclerotic lesions develop preferentially at arterial regions exposed to disturbed flow (d-flow), which induces genomic stress, endothelial injury, and barrier dysfunction. Hemodynamic forces are known to reprogram endothelial metabolism, but the role of de novo purine synthesis (DNPS), which supplies nucleotides for genome maintenance and whose terminal steps are catalyzed by the bifunctional enzyme ATIC, remains undefined in atherosclerosis. By integrating bulk and single-cell multiomics with in vitro flow systems and in vivo models, we show that d-flow upregulates DNPS and ATIC …

Apathy, Effort-Based Decisions And Brain Integrity In Alzheimer’S And Parkinson’S Diseases, Lee-Anne Morris, Hideo Suzuki, Seonjoo Lee, Zekai Jin, Bryan B Chen, Ana Marin, Edward D Huey, Yunglin Gazes, Sarah R Heilbronner, Campbell J Le Heron, Nora Vanegas-Arroyave

Faculty, Staff and Students Publications

Apathy, or loss of motivation, is a prominent syndrome accompanying both Alzheimer's and Parkinson's diseases, in addition to other disorders. One approach to understanding motivational loss is to examine the processes underlying goal-directed behaviour. Weighing up rewarding outcomes against the effort costs required to obtain them (effort-based decision-making) is a core computation when deciding to act for outcomes. Although a growing body of evidence points to disruption of this computation in people with apathy, which underlying decision parameters drive this disruption, their neural associations and whether these would generalize or differ across brain disorders have not been examined. People with …

Small Partial Deletion Of A Highly Gc-Rich Foxf1 Exon 1 In Two Deceased Siblings With Alveolar Capillary Dysplasia, Hiuling Chan Joiner, Shruti A Pande, Przemyslaw Szafranski, Partha Sen, Gail Deutsch, Pawel Stankiewicz

Faculty, Staff and Students Publications

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disorder caused by haploinsufficiency of FOXF1. While larger-sized coding and noncoding copy-number variant (CNV) deletions involving the FOXF1 locus are detected in approximately half of histopathologically-diagnosed ACDMPV patients, small CNVs remain diagnostically challenging. Here, we revisited an unsolved case of familial ACDMPV with two affected siblings. Whole genome sequencing (WGS) of 30-year-old archival lung autopsy tissue analyzed using AI powered platform revealed a 151 bp CNV deletion involving a highly GC-rich portion of exon 1 of FOXF1 that was not detected using Sanger sequencing and …

Cpt1a Loss Promotes Lung Metastasis In Immune-Competent Mice Via A Mechanism Of Mtdna Release And Chronic Activation Of Sting Pathway, Xiaoyong Wang, Shu-Ting Chou, Yoonha Hwang, Jin Chen, Deanna N Edwards

Faculty, Staff and Students Publications

The metastatic progression of breast cancer involves complex interactions between tumor cells and immune cells, including T cells that exert cytotoxic pressure to limit metastasis. Tumor cells reprogram their metabolism to evade immune surveillance, a critical step to achieving metastatic outgrowth. Using an unbiased CRISPR screen targeting metabolism-related genes and a clinically relevant spontaneous metastasis mouse model, we identified CPT1A, the rate-limiting enzyme in fatty acid β-oxidation, as a suppressor of immune-dependent metastasis. Loss of CPT1A enhances lung metastasis in immunocompetent mice, but not Rag1 KO mice that lack mature lymphocytes. Loss of CPT1A triggers cytosolic mitochondrial DNA (mtDNA) release …

Randomised Controlled Trial Comparing Antibiotic Cement Bead Pouch Versus Negative Pressure Wound Therapy For The Management Of Severe Open Tibia Fracture Wounds: Beads Versus Vac (Bvv) Protocol, Lucas S Marchand, Gerard Slobogean, Nathan N O'Hara, Anthony D Harris, David W Grainger, Lehana Thabane, Mohit Bhandari, Gregory J Della Rocca, Patrick J Kellam, Robert D Zura, Debra Marvel, Jeffrey L Wells, I Leah Gitajn, Kyle J Jeray, Robert V O'Toole, Zachary M Working, Roman M Natoli, Patrick F Bergin, Jennifer E Hagen, Ashley E Levack, Ernesto Guerra-Farfan, Gregory M Schrank, Joan N Hebden, Franca Mossuto, Cassandra Tsoutsounakis, David Pogorzelski, Hailey Pineda, Sofia Bzovsky, Sheila Sprague, Bvv Investigators

Faculty, Staff and Student Publications

Introduction: Early open fracture management aims to minimise the risk of complications. For the most severe open fracture wounds, multiple irrigation and debridement surgeries are required to overcome severe wound contamination, to reassess the evolving tissue injury or to temporise and plan further surgery. When multiple irrigation and debridement surgeries are needed, uncertainty remains about how the open fracture wound should be managed to best minimise complications. The primary aim of this trial is to compare the antibiotic cement bead pouch vs negative pressure wound therapy in the management of patients with severe open tibia fracture wounds.

Methods and analysis: …

Mogad Is The Most Common Cause Of Isolated Optic Neuritis In Children, Chaitanya Aduru, Akansha Chandrasekar, Kyla Blasingame, Jonathan Rosen, Jesse M Levine, Karla Salazar, Madhuri Chilakapati, Rod Foroozan, Victoria Hardwick, Jonathan M Yarimi, Nikita Shukla, Timothy E Lotze, Kristen S Fisher, Alexander J Sandweiss

Faculty, Staff and Students Publications

Objectives: The study aimed to characterize the clinical features, etiologies, and outcomes of isolated, first-time pediatric ON in the post-MOG-IgG era.

Methods: This was a single-center retrospective cohort study at Texas Children's Hospital of patients diagnosed with first-time ON between 2018-2024, with follow-up data collected through 2025. Inclusion criteria required monocular or binocular subacute vision loss with supportive paraclinical signs. Subjects were excluded if they had a prior history of demyelinating disease or extra-orbital demyelinating lesions on initial brain/spine MRI. Primary outcomes were the proportion of MOG-IgG seropositivity, retinal nerve fiber layer thickness, and visual acuity at onset and most …

Investigating Causal Associations Among Inflammatory Proteins, Blood Metabolites, And Alzheimer’S Disease Risk, Shuai Liu, Jingjing Zhu, Hua Zhong, Dan Zhou, Quan Long, Zichen Zhang, Xiaochen Yang, Qing Wu, Chao Cheng, Jianyong Wu, Hung N Luu, Jing Wang, Bingxin Zhao, Chong Wu, Youping Deng, Lang Wu

Faculty, Staff and Students Publications

Alzheimer's disease (AD) is a prevalent degenerative neurological disorder with limited treatment options. Prior studies reported specific metabolites and inflammatory proteins to be related to AD risk. However, the intricate relationship between inflammatory proteins, blood metabolites, and AD risk in European population remains unclear. Genetic instruments for 1,091 metabolites and 736 inflammatory proteins were derived from two recent comprehensive genome-wide association studies. Univariable Mendelian Randomization was employed to assess potential causal effects of metabolites on AD risk, potential effects of inflammatory proteins on metabolites, and effects of inflammatory proteins on AD risk. Multivariable MR (MVMR) was further applied to disentangle …